[ CAS No. 66131-68-8 ] {[proInfo.proName]}

Name: 66131-68-8|2-Chloro-N-methylpyrimidin-4-amine|97%
Brand: Ambeed
SKU: A125024
Price: 18.0 USD
Availability: InStock
Rating: 98 (29 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

DV 2D 3D

3d Animation Molecule Structure of 66131-68-8

Structure of 66131-68-8 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 66131-68-8 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 66131-68-8 ]

SDS Specification

Alternatived Products of [ 66131-68-8 ]

Product Details of [ 66131-68-8 ]

CAS No. :	66131-68-8	MDL No. :	MFCD09055368
Formula :	C₅H₆ClN₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	WJNSNVIQHYHUHX-UHFFFAOYSA-N
M.W :	143.57	Pubchem ID :	13758004
Synonyms :

Calculated chemistry of [ 66131-68-8 ]

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.2
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	36.35
TPSA :	37.81 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.13 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.57
Log Po/w (XLOGP3) :	1.48
Log Po/w (WLOGP) :	0.98
Log Po/w (MLOGP) :	0.33
Log Po/w (SILICOS-IT) :	1.24
Consensus Log Po/w :	1.12

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-2.09
Solubility :	1.17 mg/ml ; 0.00813 mol/l
Class :	Soluble
Log S (Ali) :	-1.88
Solubility :	1.89 mg/ml ; 0.0132 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.68
Solubility :	0.298 mg/ml ; 0.00207 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.61

Safety of [ 66131-68-8 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H319	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 66131-68-8 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 66131-68-8 ]
Downstream synthetic route of [ 66131-68-8 ]

[ 66131-68-8 ] Synthesis Path-Upstream 1~2

1
[ 3934-20-1 ]
[ 74-89-5 ]
[ 66131-68-8 ]

Yield	Reaction Conditions	Operation in experiment
58%	at -40 - 0℃; for 4 h;	2-Chloro-N-methylpyrimidin-4-amine (18)[00413] To a solution of 2,4-dichloropyrimidine (5.0 g, 33.79 mmol) in anhydrous THF (50 mL) was slowly added 2.0 M methylamine solution in THF (42.2 mL, 84.48 mmol) at -40 °C. The reaction mixture was stirred at 0 °C for 4 h and partitioned between CHCl₃/2- propanol (4/1) and water. The organic layer was dried over anhydrous sodium sulfate, filtered through a pad of CELITE, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (100percent dichloromethane) to afford 2-chloro-N- methylpyrimidin-4-amine (2.8 g, 58percent yield) as a white solid. Rt = 1.15 min;¹H NMR 600 MHz (DMSO-d₆) 8.02 (s, 1H), 6.22 (m, 1H), 2.86 (d, J = 4.8 Hz, 3H) ppm; MS m/z: 144.12 [M+1].
27%	at 20℃; for 3 h;	2,4-Dichloropyrimidine (104, 500 mg, 3.30 mmol) was dissolved in methanol (5 mL) having 2.0 M monomethylamine dissolved therein, stirred at room temperature for 3 hours. Then, the methanol solvent was removed under reduced pressure and water was added to the reaction mixture. Organic compounds were extracted with ethyl acetate and evaporated after a treatment with sodium sulfate. Purification was performed by column chromatograph to give the target compound 2-chloro-4-(N-monomethylamino)pyrimidine (106b, 128 mg, 27percent) as a yellow solid.¹H NMR (400 MHz, CDCl₃) δ 3.01 (d, J=5.2 Hz, 3H), 5.97 (brs, 1H), 6.55 (d, J=5.2, 1H), 8.16 (s, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 28.3, 109.6, 159.0, 162.9.

Reference： [1] Patent: WO2016/23014, 2016, A2, . Location in patent: Paragraph 00412-00413
[2] Patent: US2010/261727, 2010, A1, . Location in patent: Page/Page column 30
[3] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 13, p. 3510 - 3513
[4] Patent: WO2009/97474, 2009, A1, . Location in patent: Page/Page column 26-27
[5] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 5, p. 1349 - 1356
[6] Archiv der Pharmazie, 2014, vol. 347, # 2, p. 77 - 88

2
[ 3934-20-1 ]
[ 593-51-1 ]
[ 66131-68-8 ]

Yield	Reaction Conditions	Operation in experiment
63%	With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 18 h;	Into a 50-mL round-bottom flask, was placed 2,4-dichloropyrimidine (1.1 g, 7.38 mmol, 1.00 equiv.), methanamine hydrochloride (498 mg, 7.38 mmol, 1.00 equiv.), potassium carbonate (3.07 g, 22.21 mmol, 3.00 equiv.), N,N-dimethylformamide (10 mL). The resulting solution was stirred for 18 h at 20 °C. The resulting solution was diluted with 60 mL of H2O. The resulting solution was extracted with 3x80 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3x100 mL of brine. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/2). This resulted in 0.67 g (63percent) of 2-chloro-N- methylpyrimidin-4-amine as a white solid.

Reference： [1] Patent: WO2017/181177, 2017, A1, . Location in patent: Paragraph 0448-0450

[ 66131-68-8 ] Synthesis Path-Downstream 1~52

Yield	Reaction Conditions	Operation in experiment
	In methanol; ethanol; at 20℃; for 0.5h;Heating;	General procedure: To a 250mL round bottom flask equipped with a stir bar was added 9.0g 5-fiuoro- 2,4-dichloro- pyriniidine, 40mL methanol and 15mL of 8M methylamine in ethanol. The reaction heated up (mild exo-therm) and was allowed to stir at room temperature for -30 minutes. A check by TLC (1 :1 EtOAc: heptane) and LCMS showed complete reaction. The reaction was concentrated down to give 9.77g crude material which was purified on a silica column running a gradient of 1% to 10% MeOH in DCM over 35 minutes to give 6.77 g pure 2-chloro-5-fiuoro-N-methylpyrimidin-4- amine.The same method was used to make the compounds shown in Table 1 below, using the appropriate commercially available substituted 2,4-dichloro- pyrimidines and amines.

2
[ 3934-20-1 ]
[ 74-89-5 ]
[ 66131-68-8 ]

Yield	Reaction Conditions	Operation in experiment
58%	In tetrahydrofuran; at -40 - 0℃; for 4h;	2-Chloro-N-methylpyrimidin-4-amine (18)[00413] To a solution of 2,4-dichloropyrimidine (5.0 g, 33.79 mmol) in anhydrous THF (50 mL) was slowly added 2.0 M methylamine solution in THF (42.2 mL, 84.48 mmol) at -40 C. The reaction mixture was stirred at 0 C for 4 h and partitioned between CHCl3/2- propanol (4/1) and water. The organic layer was dried over anhydrous sodium sulfate, filtered through a pad of CELITE, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (100% dichloromethane) to afford 2-chloro-N- methylpyrimidin-4-amine (2.8 g, 58% yield) as a white solid. Rt = 1.15 min;1H NMR 600 MHz (DMSO-d6) 8.02 (s, 1H), 6.22 (m, 1H), 2.86 (d, J = 4.8 Hz, 3H) ppm; MS m/z: 144.12 [M+1].
27%	In methanol; at 20℃; for 3h;	2,4-Dichloropyrimidine (104, 500 mg, 3.30 mmol) was dissolved in methanol (5 mL) having 2.0 M monomethylamine dissolved therein, stirred at room temperature for 3 hours. Then, the methanol solvent was removed under reduced pressure and water was added to the reaction mixture. Organic compounds were extracted with ethyl acetate and evaporated after a treatment with sodium sulfate. Purification was performed by column chromatograph to give the target compound 2-chloro-4-(N-monomethylamino)pyrimidine (106b, 128 mg, 27%) as a yellow solid.1H NMR (400 MHz, CDCl3) delta 3.01 (d, J=5.2 Hz, 3H), 5.97 (brs, 1H), 6.55 (d, J=5.2, 1H), 8.16 (s, 1H); 13C NMR (100 MHz, CDCl3) delta 28.3, 109.6, 159.0, 162.9.
	With N-ethyl-N,N-diisopropylamine; In ethanol; at 100℃; for 0.166667h;Microwave irradiation;	Example 2; 1-[4-(methylamino)-2-pyrimidinyl]-lambda/-[2-(trifluoromethyl)phenyl]methyl}-4- piperidinecarboxamide; Step 1 : 2-chloro-lambda/-methyl-4-pyrimidinamine; To a solution of 2,4-dichloropyrimidine (182 mg, 1.222 mmol, 1.00 equiv) and ethanol (4.0 ml) in a microwave vial, diisopropylethylamine (1.07 ml, 6.11 mmol, 5.00 equiv) and methylamine (0.611 ml, 1.222 mmol, 1.00 equiv) were added. The reaction mixture was heated via a microwave reactor for 10 min at 1000C. The solvent was removed under reduced pressure. The compound was carried forward without purification.

Reference： [1]Patent: WO2016/23014,2016,A2 .Location in patent: Paragraph 00412-00413
[2]Organic and Biomolecular Chemistry,2019,vol. 17,p. 2020 - 2027
[3]Patent: US2010/261727,2010,A1 .Location in patent: Page/Page column 30
[4]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3510 - 3513
[5]Patent: WO2009/97474,2009,A1 .Location in patent: Page/Page column 26-27
[6]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 1349 - 1356
[7]Archiv der Pharmazie,2014,vol. 347,p. 77 - 88

3
[ 37143-54-7 ]
[ 66131-68-8 ]
N²-(2-methoxy-1-methyl-ethyl)-N⁴-methyl-pyrimidine-2,4-diamine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3510 - 3513

4
[ 24424-99-5 ]
[ 66131-68-8 ]
2-chloro-4-(tert-butoxycarbonyl-methylamino)pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With dmap; triethylamine; In tetrahydrofuran; at 70℃; for 3h;	A solution of <strong>[66131-68-8]2-chloro-N-methylpyrimidin-4-amine</strong> (500 mg, 3.4 mmol), di-tertbutyl dicarbonate (1.49 mL, 6.9 mmol), TEA (0.96 mL, 6.9 mmol), DMAP (42.5 mg, 0.34 mmol) in THF (20 mL) was stirred at 70 C for 3 h. The reation mixture was cooled, and concentrated under reduced pressure. Purification (FCC, 5i02, 0-20% EtOAc in hexanes) afforded the title compound (762 mg,88%). MS (ESI): mass calcd. for C10H14C1N302, 243.1; m/zfound, 244.0 [M+H]. 1H NMR (500 MHz, DMSO-d5) oe 8.51 (d, J = 5.9 Hz, 1 H), 7.94 (d, J =5.9 Hz, 1 H), 3.33 (s, 3H), 1 .52 (s, 9H).

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 735 - 740
[2]Patent: WO2017/139428,2017,A1 .Location in patent: Page/Page column 128; 129
[3]Journal of Medicinal Chemistry,2007,vol. 50,p. 5024 - 5033

5
[ 66131-68-8 ]
1-[2-(2-methoxy-1-methyl-ethylamino)-pyrimidin-4-yl]-1-methyl-3-o-tolyl-urea [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3510 - 3513

6
[ 749898-76-8 ]
[ 66131-68-8 ]
[ 749898-19-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium tert-butylate; In 1-methyl-pyrrolidin-2-one; at 60℃; for 20h;	Potassium t-butoxide (165MG) was added to the product of example 1 step b) (0.2g) and 2-chloro-N-methyl-4-pyrimidinamine (105MG) in NMP (3ML). THE mixture was stirred at 60 C for 20h. The resulting mixture was cooled, acidified with acetic acid (LML) and purified by reverse phase HPLC (Symmetry gradient 90-50% aqueous, ammonium acetate (0.2% aq. ) in acetonitrile) to give the title compound as a solid (40mg). MS (APCI+) 383 [M+H] + H NMR 8 (DMSO 9O O 8.32 (d, lH), 7.82 (d, LH), 7.68 (dd, LH), 6.97 (s, LH), 6.81 (d, lH), 6.08 (d, LH), 5.15 (heptet, 1H), 4.05-3. 97 (m, 2H), 3.51-3. 44 (m, 4H), 3.43-3. 36 (m, 2H), 2.78 (d, 3H), 2.07-2. 00 (m, 2H), 1.87-1. 82 (m, 4H), 1.73-1. 63 (m, 2H)

Reference： [1]Patent: WO2004/74278,2004,A1 .Location in patent: Page 33

Yield	Reaction Conditions	Operation in experiment
		REFERENTIAL EXAMPLE 1 4-Methylamino-2-(4-phenylpiperidino)pyrimidine (compound No. 1024): To a solution of 17.0 g (0.11 mole) of 2,4-dichloropyrimidine in 150 ml of dichloromethane was added methylamine (0.25 mole, 20 ml of 40 % methanol solution) at such a rate that the temperature of the solution was maintained at 5 C. After the addition, the solution was stirred at room temperature for 12 hours. The reaction mixture was concentrated under reduced pressure, and extracted with dichloromethane. The dichloromethane layer was dried over an anhydrous sodium sulfate, and concentrated under reduced pressure to give 14.0 g (purity 80 %) of 2-chloro-4-methylaminopyrimidine.

9
[ 1141894-80-5 ]
[ 66131-68-8 ]
[ 1176772-24-9 ]

Yield	Reaction Conditions	Operation in experiment
8.2%	With N-ethyl-N,N-diisopropylamine; In ethanol; at 150℃; for 0.416667h;Microwave irradiation;	Step 2: 1 -r4-(methylamino)-2-pyrimidinyll-lambda/-{r2-(trifluoromethyl)phenyllmethyl}-4- piperidinecarboxamide; To a solution of 2-chloro-lambda/-methyl-4-pyrimidinamine (1.222 mmol, 1.00 equiv) and ethanol (5.0 ml) in a microwave vial, diisopropylethylamine (642 Dl, 3.666 mmol, 3.00 equiv) and /V-[2-(trifluoromethyl)phenyl]methyl}-4-piperidinecarboxamide (350 mg, 1.222 mmol, 1.00 equiv) were added. The reaction mixture was heated via a microwave reactor for 25 minutes at 15O0C. The solvent was removed under reduced pressure. The residue was dissolved in 2.0 ml DMSO and purified via reverse-phase HPLC purification to afford the title compound (39.4 mg, 8.2%). Structure confirmation (full 1 H and partial 13C assignment) was based on 2-D NMR data. MS (ES+): m/e 395 [M + H]+

Reference： [1]Patent: WO2009/97474,2009,A1 .Location in patent: Page/Page column 27

10
[ 6278-73-5 ]
[ 66131-68-8 ]
N₂-(4-benzothiazol-2-yl-phenyl)-N₄-methyl-pyrimidine-2,4-diamine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 1349 - 1356

11
[ 66131-68-8 ]
N2-(2-aminoethyl)-N4-methylpyrimidine-2,4-diamine [ No CAS ]

Reference： [1]Archiv der Pharmazie,2014,vol. 347,p. 77 - 88

12
[ 57260-73-8 ]
[ 66131-68-8 ]
C₁₃H₂₃N₅O₂ [ No CAS ]

Reference： [1]Archiv der Pharmazie,2014,vol. 347,p. 77 - 88

13
[ 66131-68-8 ]
1-(2-[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}pyrimidin-4-yl)-1,3,3-trimethylurea [ No CAS ]

Reference： [1]Patent: US2016/83365,2016,A1

14
[ 876-99-3 ]
[ 66131-68-8 ]
2,6-dimethylphenyl (2-chloropyrimidin-4-yl)(methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20℃; for 24h;	2,6-Dimethylphenyl (2-chloropyrimidin-4-yl)(methyl)carbamate (19)[00414] To a solution <strong>[66131-68-8]2-chloro-N-methylpyrimidin-4-amine</strong> (1.0 g, 6.99 mmol) and N,N-diisopropylethylamine (3.65 mL, 20.97 mmol) in tetrahydrofuran (10 mL) was added 2,6-dimethylphenyl chloroformate (1.92 g, 10.49 mmol). The resulting mixture was stirred at room temperature for 24 h and diluted with ethyl acetate. The resulting mixture was partitioned between ethyl acetate and saturated aqueous sodium carbonate solution. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered with a pad of CELITE, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (0/100 to 1/97, methanol/dichloromethane) to afford 2,6- dimethylphenyl (2-chloropyrimidin-4-yl)(methyl)carbamate (1.65 g, 81% yield) as a white solid. Rt = 3.87 min;1H NMR 600 MHz (CDCl3) 8.36 (d, J = 6.0 Hz, 1H), 8.06 (d, J = 6.0 Hz, 1H), 7.03 (m, 3H), 3.68 (s, 3H), 2.14 (s, 6H) ppm; MS m/z: 292.24 [M+1].

Reference： [1]Patent: WO2016/23014,2016,A2 .Location in patent: Paragraph 00412; 00414

15
[ 876-99-3 ]
[ 66131-68-8 ]
2,6-dimethylphenyl (2-chloropyrimidin-4-yl)(methyl)carbamate [ No CAS ]

Reference： [1]Patent: WO2016/23014,2016,A2

16
[ 66131-68-8 ]
[ 79-44-7 ]
1-(2-chloropyrimidin-4-yl)-1,3,3-trimethylurea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of <strong>[66131-68-8]2-chloro-N-methylpyrimidin-4-amine</strong> (0.25 g, 1.741 mmol) in DMF (17.41 mL) at 0 C. was added 60% NaH in oil (0.139 g, 3.48 mmol). The reaction mixture was stirred at 0 C. for 30 minutes and dimethylcarbamic chloride (0.160 mL, 1.741 mmol) was then added. The reaction was allowed to warm to room temperature and was stirred at room temperature for 1 hour. The reaction mixture was then poured on ice/water (50 mL) and extracted with EtOAc (3*20 mL). The combined organic phases were dried over MgSO4, and the volatiles were removed under reduced pressure. The crude material was purified by SiO2 column chromatography (50 g SNAP column, 0% MeOH/DCM for 5 minutes, 0-5% MeOH/DCM for 25 minutes, and 5-10% MeOH/DCM for 10 minutes to afford 1-(2-chloropyrimidin-4-yl)-1,3,3-trimethylurea.

Reference： [1]Patent: US2016/83365,2016,A1 .Location in patent: Paragraph 0876; 0877; 0878

17
[ 66131-68-8 ]
N²-(3-bromo-2-chlorobenzo[b]thiophen-5-yl)-N⁴-methylpyrimidine-2,4-diamine [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 735 - 740

18
[ 66131-68-8 ]
5-(6-chloro-5-(2-chloro-5-((4-(methylamino)pyrimidin-2-yl)amino)benzo[b]thiophen-3-yl)pyridin-3-yl)-3,6-dimethylpyrimidin-4(3H)-one [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 735 - 740

19
2-(5-chloro-2,4-dimethoxyphenyl)-7-(piperazin-1-yl)imidazo[1,2-a]pyridine [ No CAS ]
[ 66131-68-8 ]
2-(4-(2-(5-chloro-2,4-dimethoxyphenyl)imidazo[1,2-a]pyridin-7-yl)piperazin-1-yl)-N-methylpyrimidin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
8%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 100℃; for 16h;Sealed tube;	A solution of 2-(5-chloro-2,4-dimethoxyphenyl)-7-(piperazin-1-yl)imidazo[1,2-a]pyridine 301 (200 mg, 0.53 mmol) and N,N-diisopropylethylamine (0.4 mL, 2.29 mmol) in DMF (5 mL) was charged with <strong>[66131-68-8]2-chloro-N-methylpyrimidin-4-amine</strong> ( 155 mg, 1.07 mmol). The reaction mixture was stirred at 100 C for 16 h. The reaction mixture was cooled to room temperature, suspended in water and stirred for 1 h. The precipitate was collected by filtration; the solid obtained was washed with water, dried under reduced pressure and purified by combi-fash companion (silica gel, CH3OH/CH2Cl2). The product was further triturated with methanol and filtered. The solids were washed with hexanes and dried to provide 2-(4-(2-(5-chloro-2,4-dimethoxyphenyl)imidazo[1,2-a]pyridin-7-yl)piperazin-1-yl)-N-methylpyrimidin-4-amine 418a (20 mg, 8%) as light brown solid. 1H NMR (300 MHz, DMSO-d6) delta 8.34 i d . ./ 7.5 Hz, 1H), 8.15 (s, 1H), 8.04 (s, 1H), 7.75 (br s, 1H), 6.97 (br s, I I I ) . 6.89 (s, IH), 6,87 (s, 1H), 6,71 (s, i l l ). 5.78 (d, ./ 5,7 Hz, 1H), 4.01 (s, 3H), 3.93 (s, 3H), 3.83 (br s, 4H), 3.33 (br s, 4H), 2,78 (d, ,/ 4.2 Hz, 3H): HPLC (Method 1 ) 92.8% (AUC), fR = 1 1.85 min.; ESI+APCI MS m/z 480 [M + Hf.

Reference： [1]Patent: WO2017/58503,2017,A1 .Location in patent: Page/Page column 419; 420

20
1-(5-amino-2-methoxyphenoxy)-3-(pyrrolidin-1-yl)propan-2-ol [ No CAS ]
[ 66131-68-8 ]
(R)-1-(2-methoxy-5-((4-(methylamino)pyrimidin-2-yl)amino)phenoxy)-3-(pyrrolidin-1-yl)propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
5%	With trifluoroacetic acid; In isopropyl alcohol; at 90℃; for 3h;	Into a 50-mL round-bottom flask, was placed l-(5-amino-2-methoxyphenoxy)-3- (pyrrolidin-l-yl)propan-2-ol (600 mg, 1 equiv), <strong>[66131-68-8]2-chloro-N-methylpyrimidin-4-amine</strong> (324 mg, 2.26 mmol, 1 equiv), isopropanol (10 mL), trifluoroacetic acid (514 mg, 4.55 mmol, 2.00 equiv). The resulting solution was stirred for 3 h at 90C in an oil bath. The resulting mixture was concentrated under vacuum. The crude product was purified by Chiral-Prep-HPLC ID. This resulted in 42 mg (5%) of l-(5-amino-2-methoxyphenoxy)-3-(pyrrolidin-l-yl)propan-2- ol (600 mg, 1 equiv), <strong>[66131-68-8]2-chloro-N-methylpyrimidin-4-amine</strong> as a light yellow solid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 0767; 0777-0778

21
1-(5-amino-2-methoxyphenoxy)-3-(pyrrolidin-1-yl)propan-2-ol [ No CAS ]
[ 66131-68-8 ]
(S)-1-(2-methoxy-5-((4-(methylamino)pyrimidin-2-yl)amino)phenoxy)-3-(pyrrolidin-1-yl)propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
5%	With trifluoroacetic acid; In isopropyl alcohol; at 90℃; for 2h;	Into a 50-mL round-bottom flask, was placed l -(5-amino-2-methoxyphenoxy)-3- (pyrrolidin-l-yl)propan-2-ol (600 mg, 2.25 mmol, 1 equiv), 2-chloro-N-methylpyrimidin-4- amine (324 mg, 2.26 mmol, 1 equiv), isopropanol (10 mL), trifluoroacetic acid (514 mg, 4.55 mmol, 2.00 equiv). The resulting solution was stirred for 2 h at 90 C in an oil bath. The resulting mixture was concentrated under vacuum. The crude product was purified by Chiral- Prep-HPLC IB4. This resulted in 41.1 mg (5%) of (S)-l -(2-methoxy-5-((4- (methylandno)pyrinddin-2-yl)amino)phenoxy)-3-(pyrrolidin-l-yl)propan-2-ol as a light yellow solid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 0779-0781

22
4-methoxy-3-((1-methylpyrrolidin-3-yl)methoxy)aniline [ No CAS ]
[ 66131-68-8 ]
(S)-N2-(4-methoxy-3-((1-methylpyrrolidin-3-yl)methoxy)phenyl)-N4-methylpyrimidine-2,4-diamine [ No CAS ]
(R)-N2-(4-methoxy-3-((1-methylpyrrolidin-3-yl)methoxy)phenyl)-N4-methylpyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With trifluoroacetic acid; In isopropyl alcohol; at 90℃; for 3h;	Into a 100-mL round-bottom flask, was placed 4-methoxy-3-[(l- methylpyrrolidin-3-yl)methoxy]aniline (300 mg, 1.27 mmol, 1 equiv), trifluoroacetic acid (290 mg, 2.57 mmol, 2.00 equiv, 98%), <strong>[66131-68-8]2-chloro-N-methylpyrimidin-4-amine</strong> (182 mg, 1.27 mmol, 1 equiv), isopropanol (15 mL). The resulting solution was stirred for 3 h at 90 C in an oil bath. The resulting mixture was concentrated under vacuum. The crude product was applied onto a silica gel column with NH4HC03:ACN (1 : 1), Detector, UV 254 nm. This resulted in 23 mg (5%) of (S)-N2-(4-methoxy-3-((l-methylpyrrolidin-3-yl)methoxy)phenyl)- N4-methylpyrimidine-2,4-diamine El (arbitrarily assigned, S) and 22.7 mg (5%) of (R)-N2- (4-methoxy-3-((l-methylpyrrolidin-3-yl)methoxy)phenyl)-N4-methylpyrimidine-2,4-di amine E2 (arbitrarily assigned, R) as a white solid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 01068; 01078-01079

23
3-[3-(pyrrolidino)propoxy]benzenamine [ No CAS ]
[ 66131-68-8 ]
N4-methyl-N2-(3-(3-(pyrrolidin-1-yl)propoxy)phenyl)pyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
18%	With toluene-4-sulfonic acid; In isopropyl alcohol; at 85℃; for 2h;	Into a 50-mL round-bottom flask, was placed 3-[3-(pyrrolidin-l-yl)propoxy]aniline (400 mg, 1.82 mmol, 1 equiv), <strong>[66131-68-8]2-chloro-N-methylpyrimidin-4-amine</strong> (259 mg, 1.80 mmol, 1 equiv), 4-methylbenzene-l -sulfonic acid (464 mg, 2.69 mmol, 1.50 equiv), isopropanol (10 mL). The resulting solution was stirred for 2 h at 85 C. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ACN/H20 (1/5). This resulted in 104.7 mg (18%) of N4-methyl-N2-(3-(3-(pyrrolidin-l- yl)propoxy)phenyl)pyrimidine-2,4-diamine as a white solid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 0529; 0536-0537

24
3-[3-(pyrrolidin-1-yl)propoxy]cyclohexan-1-amine [ No CAS ]
[ 66131-68-8 ]
N4-methyl-N2-((1R,3S)-3-(3-(pyrrolidin-1-yl)propoxy)cyclohexyl)pyrimidine-2,4-diamine [ No CAS ]
N4-methyl-N2-((1S,3R)-3-(3-(pyrrolidin-1-yl)propoxy)cyclohexyl)pyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; In isopropyl alcohol; at 110℃; for 12h;	Into a 30-mL pressure tank reactor, was placed <strong>[66131-68-8]2-chloro-N-methylpyrimidin-4-amine</strong> (550 mg, 3.83 mmol, 1.20 equiv), 3-[3-(pyrrolidin-1-yl)propoxy]cyclohexan-1-amine (720 mg, 3.18 mmol, 1 equiv), PTSA (1 g, 5.81 mmol, 2.00 equiv), IPA (10 mL). The resulting solution was stirred for 12 h at 110 C in an oil bath. The resulting mixture was concentrated under vacuum. The crude product was purified by Flash-Prep-HPLC A MeOH. The crude product 120mg was purified by Chiral-Prep-HPLC This resulted in 42.6 mg (3%) of enantiomer 1 (randomly assigned) as yellow oil and 32.0 mg (2%) enantiomer 2 (randomly assigned) as an oil.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 0630; 0634-0635

25
7-amino-2-[2-(pyrrolidin-1-yl)ethyl]-1,2,3,4-tetrahydroisoquinolin-1-one [ No CAS ]
[ 66131-68-8 ]
7-((4-(methylamino)pyrimidin-2-yl)amino)-2-(2-(pyrrolidin-1-yl)ethyl)-3,4-dihydroisoquinolin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	With trifluoroacetic acid; In isopropyl alcohol; at 85℃; for 4h;	Into a 25-mL round-bottom flask, was placed 7-amino-2-[2-(pyrrolidin-l-yl)ethyl]- 1,2,3,4-tetrahydroisoquinolin-l-one (60 mg, 0.23 mmol, 1 equiv), 2-chloro-N- methylpyrimidin-4-amine (34 mg, 0.24 mmol, 1 equiv), isopropanol (6 mL), trifluoroacetic acid (52 mg, 0.46 mmol, 2.00 equiv). The resulting solution was stirred for 4 h at 85 C in an oil bath. The resulting mixture was concentrated under vacuum. The crude product was purified by Prep-HPLC C TFA. This resulted in 45.3 mg (41%) of the title compound as a solid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 0642; 0646-0647

26
3-[2-fluoro-3-(pyrrolidin-1-yl)propoxy]aniline [ No CAS ]
[ 66131-68-8 ]
N2-(3-(2-fluoro-3-(pyrrolidin-1-yl)propoxy)phenyl)-N4-methylpyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
11%	With trifluoroacetic acid; In isopropyl alcohol; at 85℃;	Into a 8-mL round-bottom flask, was placed <strong>[66131-68-8]2-chloro-N-methylpyrimidin-4-amine</strong> (120 mg, 0.84 mmol, 1 equiv), 3-[2-fluoro-3-(pyrrolidin-l-yl)propoxy]aniline (80 mg, 0.34 mmol, 0.40 equiv), trifluoroacetic acid (0.2 mL), isopropanol (3 mL). The resulting solution was stirred overnight at 85 C. The crude product was purified by Prep-HPLC C TFA. This resulted in 37.4 mg (11%) of N2-(3-(2-fluoro-3-(pyrrolidin-l-yl)propoxy)phenyl)-N4- methylpyrimidine-2,4-diamine as a white solid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 0675; 0682-0683

27
3-[2,2-difluoro-3-(pyrrolidin-1-yl)propoxy]aniline [ No CAS ]
[ 66131-68-8 ]
N2-(3-(2,2-difluoro-3-(pyrrolidin-1-yl)propoxy)phenyl)-N4-methylpyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%	With trifluoroacetic acid; In isopropyl alcohol; at 80℃; for 4h;	Into a 50-mL round-bottom flask, was placed 3-[2,2-difluoro-3-(pyrrolidin-1-yl)propoxy] aniline (40 mg, 0.16 mmol, 1 equiv), trifluoroacetic acid (35 mg, 0.31 mmol, 2.00 equiv), isopropanol (10 mL), <strong>[66131-68-8]2-chloro-N-methylpyrimidin-4-amine</strong> (27 mg, 0.19 mmol, 1.20 equiv). The resulting solution was stirred for 4 h at 80 C in an oil bath. The resulting mixture was concentrated under vacuum. The crude product was purified by Prep-HPLC F TFA. This resulted in 39.2 mg (53%) of N2-(3-(2,2-difluoro-3-(pyrrolidin-1-yl)propoxy)phenyl)-N4-methylpyrimidine-2,4-diamine as a white solid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 0684; 0700-0701

28
3-[1-[2-(pyrrolidin-1-yl)ethoxy]ethyl]aniline [ No CAS ]
[ 66131-68-8 ]
N4-methyl-N2-(3-(1-(2-(pyrrolidin-1-yl)ethoxy)ethyl)phenyl)pyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	With trifluoroacetic acid; In isopropyl alcohol; at 90℃; for 3h;	Into a 100-mL round-bottom flask, was placed 3-[l-[2-(pyrrolidin-l- yl)ethoxy] ethyl] aniline (350 mg, 1.49 mmol, 1 equiv), <strong>[66131-68-8]2-chloro-N-methylpyrimidin-4-amine</strong> (214 mg, 1.49 mmol, 1 equiv), isopropanol (20 mL), trifiuoroacetic acid (341 mg, 3.02 mmol, 2.00 equiv). The resulting solution was stirred for 3 h at 90 C in an oil bath. The resulting mixture was concentrated under vacuum. The crude product was purified by Prep-HPLC C TFA. This resulted in 171.5 mg (25%) of N4-methyl-N2-(3-(l-(2-(pyrrolidin-l- yl)ethoxy)ethyl)phenyl) pyrimidine-2,4-diamine as a semisolid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 0702; 0712-0713

29
4-methoxy-3-[3-(pyrrolidin-1-yl)propoxy]aniline [ No CAS ]
[ 66131-68-8 ]
2-N-[4-methoxy-3-[3-(pyrrolidin-1-yl)propoxy]phenyl]-4-N-methylpyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
13%	With toluene-4-sulfonic acid; In isopropyl alcohol; at 85℃; for 3h;	Into a 50-mL round-bottom flask, was placed <strong>[66131-68-8]2-chloro-N-methylpyrimidin-4-amine</strong> (200 mg, 1.39 mmol, 1.00 equiv.), 4-methoxy-3-[3-(pyrrolidin-l-yl)propoxy]aniline (350 mg, 1.40 mmol, 1.00 equiv.), 4-methylbenzene-l -sulfonic acid (476 mg, 2.76 mmol, 2.00 equiv.), isopropanol (10 mL). The resulting solution was stirred for 3 h at 85 C. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ACN/H20 (1/5). This resulted in 66.3 mg (13%) of 2-N-[4-methoxy-3-[3-(pyrrolidin-l- yl)propoxy]phenyl]-4-N-methylpyrimidine-2,4-diamine as a pink solid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 0448; 0451-0452

30
4-methoxy-3-[2-(1-methylpyrrolidin-2-yl)ethoxy]aniline [ No CAS ]
[ 66131-68-8 ]
N2-(4-methoxy-3-(2-(1-methylpyrrolidin-2-yl)ethoxy)phenyl)-N4-methylpyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	With toluene-4-sulfonic acid; In isopropyl alcohol; at 85℃; for 2h;	Into a 100-mL round-bottom flask, was placed isopropanol (10 mL), 2-chloro-N- methylpyrimidin-4-amine (252 mg, 1.76 mmol, 1 equiv), 4-methoxy-3-[2-(1-methylpyrrolidin-2-yl)ethoxy]aniline (440 mg, 1.76 mmol, 1 equiv), PTSA (303 mg, 1.76 mmol, 1 equiv). The resulting solution was stirred for 2 h at 85 C. The crude product (600 mg) was purified by Prep-HPLC D HC1. 310 mg product was obtained. This resulted in 310 mg (45%) of N2-(4-methoxy-3-(2-(l-methylpyrrolidin-2-yl)ethoxy)phenyl)-N4- methylpyrimidine-2,4-diamine as light yellow oil.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 0729; 0736-0737

31
4-methoxy-3-[(1-methylpyrrolidin-2-yl)methoxy]aniline [ No CAS ]
[ 66131-68-8 ]
N2-(4-methoxy-3-((1-methylpyrrolidin-2-yl)methoxy)phenyl)-N4-methylpyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
13%	With trifluoroacetic acid; In isopropyl alcohol; at 85℃; for 6h;	Into a 50-mL round-bottom flask, was placed 4-methoxy-3-[(1-methylpyrrolidin-2-yl)methoxy] aniline (350 mg, 1.48 mmol, 1 equiv), trifluoroacetic acid (338 mg, 2.99 mmol, 2.00 equiv), <strong>[66131-68-8]2-chloro-N-methylpyrimidin-4-amine</strong> (212 mg, 1.48 mmol, 1 equiv), propan-2- ol (10 mL). The resulting solution was stirred for 6 h at 85 C in an oil bath. The resulting mixture was concentrated under vacuum. The crude product (200 mg) was purified by Prep- HPLC C NH3. This resulted in 64.7 mg (13%) of 4-methoxy-3-[(l-methylpyrrolidin-2- yl)methoxy] aniline as an off-white solid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 0738; 0747-0748

32
4-amino-N-ethylpyridine-2-carboxamide [ No CAS ]
[ 66131-68-8 ]
N-ethyl-4-((4-(methylamino)pyrimidin-2-yl)amino)picolinamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
8%	With palladium diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100℃; for 24h;	Into a 50-mL round-bottom flask, was placed 4-amino-N-ethylpyridine-2- carboxamide (200 mg, 1.21 mmol, 1 equiv), 2-chloro-N-methylpyrirnidin-4-amine (174 mg, 1.21 mmol, 1 equiv), Xantphos (140.3 mg, 0.24 mmol, 0.20 equiv), DBU (368.5 mg, 2.42 mmol, 2.00 equiv), dioxane (10 mL), Pd(OAc)2 (27.1 mg, 0.12 mmol, 0.10 equiv). The resulting solution was stirred for 24 h at 100 C in an oil bath. The resulting solution was extracted with 3x10 mL of water and the organic layers combined. The crude product was purified by (ACN/H2O=l/20). This resulted in 30.2 mg (8%) of N-ethyl-4-((4- (methylandno)pyrinddin-2-yl)amino)picolinamide as a white solid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 0752; 0759-0760

33
[ 3934-20-1 ]
[ 593-51-1 ]
[ 66131-68-8 ]

Yield	Reaction Conditions	Operation in experiment
63%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 18h;	Into a 50-mL round-bottom flask, was placed 2,4-dichloropyrimidine (1.1 g, 7.38 mmol, 1.00 equiv.), methanamine hydrochloride (498 mg, 7.38 mmol, 1.00 equiv.), potassium carbonate (3.07 g, 22.21 mmol, 3.00 equiv.), N,N-dimethylformamide (10 mL). The resulting solution was stirred for 18 h at 20 C. The resulting solution was diluted with 60 mL of H2O. The resulting solution was extracted with 3x80 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3x100 mL of brine. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/2). This resulted in 0.67 g (63%) of 2-chloro-N- methylpyrimidin-4-amine as a white solid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 0448-0450

34
4-cyclopropyl-3-[3-(pyrrolidin-1-yl)propoxy]aniline [ No CAS ]
[ 66131-68-8 ]
N2-(4-cyclopropyl-3-(3-(pyrrolidin-1-yl)propoxy)phenyl)-N-methylpyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21.9 mg	With trifluoroacetic acid; In isopropyl alcohol; at 80℃;	Into a 50-mL round-bottom flask, was placed 4-cyclopropyl-3-[3-(pyrrolidin-l- yl)propoxy] aniline (300 mg, 1.15 mmol, 1 equiv), <strong>[66131-68-8]2-chloro-N-methylpyrimidin-4-amine</strong> (166 mg, 1.16 mmol, 1 equiv), CF3COOH (263 mg, 2.31 mmol, 2.00 equiv), isopropanol (5 mL). The resulting solution was stirred for overnight at 80 C in an oil bath. The resulting mixture was concentrated under vacuum. The crude product was purified by Prep-HPLC C TFA. This resulted in 21.9 mg of N2-(4-cyclopropyl-3-(3-(pyrrolidin-l-yl)propoxy)phenyl)-N4- methylpyrimidine-2,4-diamine as a white solid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 0872-0874

35
3-[3-(pyrrolidin-1-yl)propoxy]-4-(trifluoromethoxy)aniline [ No CAS ]
[ 66131-68-8 ]
N4-methyl-N2-(3-(3-(pyrrolidin-1-yl)propoxy)-4-(trifluoromethoxy)phenyl)pyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
17%	With trifluoroacetic acid; In isopropyl alcohol; at 80℃; for 4h;	Into a 50-mL round-bottom flask, was placed 3-[3-(pyrrolidin-l-yl)propoxy]-4- (trifluoromethoxy)aniline (350 mg, 1.15 mmol, 1 equiv), 2-chloro-N-methylpyrimidin-4- amine (164.7 mg, 1.15 mmol, 1 equiv), trifluoroacetic acid (262.5 mg, 2.32 mmol, 2.00 equiv), isopropanol (6 mL). The resulting solution was stirred for 4 h at 80 C in an oil bath. The resulting mixture was concentrated under vacuum. The crude product (450 mg) was purified by Prep-HPLC C NH3. This resulted in 104 mg (17%) of N4-methyl-N2-(3-(3- (pyrrolidin-l-yl)propoxy)-4-(trifluoromethoxy)phenyl)pyrinddine-2,4-diamine as a white solid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 0875; 0888-0889

36
[ 854923-03-8 ]
[ 66131-68-8 ]
N2-(1-(3-(dimethylamino)propyl)-1H-indazol-6-yl)-N4-methylpyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
14%	With toluene-4-sulfonic acid; In isopropyl alcohol; at 80℃; for 12h;	Into a 20-mL vial, was placed isopropanol (2 mL), 2-[3-(dimethylamino)propyl]-2H-indazol-6-amine (150 mg, 0.69 mmol, 1 equiv), 2-chloro-N- methylpyrimidin-4-amine (109 mg, 0.76 mmol, 1.10 equiv), PTSA (118 mg, 0.69 mmol, 1 equiv). The resulting solution was stirred for 12 h at 80 C. The resulting mixture was concentrated under vacuum. The crude product (100 mg) was purified by Prep-HPLC G. This resulted in 35.1 mg (14%) of N2-(l-(3-(dimethylamino)propyl)-lH-indazol-6-yl)-N4-methylpyrimidine-2,4-diamine as a yellow solid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 01015; 01022-01023

37
[ 104177-48-2 ]
[ 66131-68-8 ]
N2-(2-(2-(dimethylamino)ethyl)-2H-indazol-6-yl)-N4-methylpyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
12%	With trifluoroacetic acid; In isopropyl alcohol; at 80℃; for 2h;	Into a 50-mL round-bottom flask, was placed 2-[2-(dimethylamino)ethyl]-2H- indazol-6-amine (370 mg, 1.81 mmol, 1 equiv), isopropanol (5 mL), trifluoroacetic acid (414 mg, 3.63 mmol, 2.00 equiv), <strong>[66131-68-8]2-chloro-N-methylpyrimidin-4-amine</strong> (259 mg, 1.80 mmol, 1 equiv). The resulting solution was stirred for 2 h at 80 C. The crude product was purified by Prep-HPLC F HCl. This resulted in 73 mg (12%) of N2-(2-(2-(dimethylamino)ethyl)-2H- indazol-6-yl)-N4-methylpyrimidine-2,4-diamine as a light yellow solid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 01024; 01031-01032

38
4-methoxy-3-[[(1-methylpyrrolidin-3-yl)oxy]methyl]aniline [ No CAS ]
[ 66131-68-8 ]
N2-(4-methoxy-3-(((1-methylpyrrolidin-3-yl)oxy)methyl)phenyl)-N4-methylpyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49 mg	With trifluoroacetic acid; In isopropyl alcohol; at 85℃; for 12h;	Into a 50-mL round-bottom flask, was placed 4-methoxy-3-[[(l- methylpyrrolidin-3-yl)oxy]methyl]aniline (200 mg, 0.85 mmol, 1 equiv), 2-chloro-N- methylpyrimidin-4-amine (121.2 mg, 0.84 mmol, 1 equiv), isopropanol (5 mL), trifluoroacetic acid (193.2 mg, 1.71 mmol, 2.00 equiv). The resulting solution was stirred for 12 h at 85 C in an oil bath. The crude product was purified by Prep-HPLC C HC1. This resulted in 49.0 mg (15%) of N2-(4-methoxy-3-(((l-methylpyrrolidin-3- yl)oxy)methyl)phenyl)-N4-methylpyrimidine-2,4-diamine as an oil.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 01033; 01040-01041

39
4-methoxy-3-[(1-methylpiperidin-3-yl)methoxy]aniline [ No CAS ]
[ 66131-68-8 ]
N2-(4-methoxy-3-((1-methylpiperidin-3-yl)methoxy)phenyl)-N4-methylpyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20%	With trifluoroacetic acid; In isopropyl alcohol; at 85℃; for 12h;	Into a 50-mL round-bottom flask, was placed 4-methoxy-3-[(l- methylpiperidin-3-yl)methoxy]aniline (300 mg, 1.20 mmol, 1 equiv), 2-chloro-N- methylpyrimidin-4-amine (170.9 mg, 1.19 mmol, 1 equiv), isopropanol (5 mL), trifluoroacetic acid (272.5 mg, 2.41 mmol, 2.00 equiv). The resulting solution was stirred for 12 h at 85 C in an oil bath. The crude product was purified by Prep-HPLC C HCI. This resulted in 93.5 mg (20%) of N2-(4-methoxy-3-((l-methylpiperidin-3-yl)methoxy)phenyl)- N4-methylpyrimidine-2,4-diamine as an off-white solid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 01051; 01060-01061

40
4-ethoxy-3-[3-(pyrrolidin-1-yl)propoxy]aniline [ No CAS ]
[ 66131-68-8 ]
N2-(4-ethoxy-3-(3-(pyrrolidin-1-yl)propoxy)phenyl)-N-methylpyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23%	With trifluoroacetic acid; In isopropyl alcohol; at 80℃; for 2h;	Into a 50-mL round-bottom flask, was placed 4-ethoxy-3-[3-(pyrrolidin-l- yl)propoxy] aniline (250 mg, 0.95 mmol, 1 equiv), <strong>[66131-68-8]2-chloro-N-methylpyrimidin-4-amine</strong> (135.4 mg, 0.94 mmol, 1 equiv), propan-2-ol (5 mL), trifluoroacetic acid (275.6 mg, 2.44 mmol, 3.00 equiv). The resulting solution was stirred for 2 h at 80vC in an oil bath. The resulting mixture was concentrated under vacuum. The crude product (250 mg) was purified by Prep-HPLC C HC1. This resulted in 87.6 mg (23%) of N2-(4-ethoxy-3-(3-(pyrrolidin-l- yl)propoxy)phenyl)-N4-methylpyrimidine-2,4-diamine as a white solid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 01154-01156

41
3-[2-(cyclopentyloxy)ethoxy]-4-methoxyaniline [ No CAS ]
[ 66131-68-8 ]
N2-(3-(2-(cyclopentyloxy)ethoxy)-4-methoxyphenyl)-N4-methylpyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	With trifluoroacetic acid; In isopropyl alcohol; at 80℃; for 2h;	Into a 20-mL vial, was placed isopropanol (2 mL), 3-[2-(cyclopentyloxy)ethoxy]-4-methoxyaniline (150 mg, 0.60 mmol, 1 equiv), 2-chloro-N- methylpyrimidin-4-amine (103 mg, 0.72 mmol, 1.20 equiv), trifluoroacetic acid (136 mg, 1.20 mmol, 2.02 equiv). The resulting solution was stirred for 2 h at 80 C. The crude product was purified by Prep-HPLC B TFA. This resulted in 124.7 mg (44%) of N2-(3-(2-(cyclopentyloxy)ethoxy)-4-methoxyphenyl)-N4-methylpyrimidine-2,4-diamine as a white solid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 01217-01219

42
3-(2-cyclopropoxyethoxy)-4-methoxyaniline [ No CAS ]
[ 66131-68-8 ]
N2-(3-(2-cyclopropoxyethoxy)-4-methoxyphenyl)-N4-methylpyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
16%	With trifluoroacetic acid; In isopropyl alcohol; at 85℃; for 5h;	Into a 50-mL round-bottom flask, was placed 3-(2-cyclopropoxyethoxy)-4- methoxy aniline (200 mg, 0.90 mmol, 1 equiv), trifluoroacetic acid (306.7 mg, 2.71 mmol, 3.00 equiv), IP A (10 mL), <strong>[66131-68-8]2-chloro-N-methylpyrimidin-4-amine</strong> (129 mg, 0.90 mmol, 1 equiv). The resulting solution was stirred for 5 h at 85 C in an oil bath. The resulting mixture was concentrated under vacuum. The crude product (200 mg) was purified by Prep-HPLC D TFA. This resulted in 65 mg (16%) of N2-(3-(2-cyclopropoxyethoxy)-4-methoxyphenyl)-N4- methylpyrimidine-2,4-diamine as a white solid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 01259; 01263-01264

43
[ 144243-24-3 ]
[ 66131-68-8 ]
N4-methyl-N2-(piperidin-3-yl)pyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With trifluoroacetic acid; In isopropyl alcohol; at 90℃; for 16h;	Into a 50-mL round-bottom flask, was placed 2-chloro-N-methylpyrimidin-4- amine (150 mg, 1.04 mmol, 1 equiv), tert-butyl 3-aminopiperidine-l-carboxylate (220 mg, 1.10 mmol, 1.05 equiv), trifluoroacetic acid (380 mg, 3.36 mmol, 3.00 equiv), IPA (5 mL). The resulting solution was stirred for 16 h at 90 C in an oil bath. The crude product was purified by Prep-HPLC C NH4HCO3. This resulted in 132.4 mg (61%) of N4-methyl-N2- (piperidin-3-yl)pyrimidine-2,4-diamine as a white powder.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 01349-01351

44
[ 87120-72-7 ]
[ 66131-68-8 ]
N4-methyl-N2-(piperidin-4-yl)pyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
19%	With trifluoroacetic acid; In isopropyl alcohol; at 90℃; for 16h;	Into a 50-mL round-bottom flask, was placed 2-chloro-N-methylpyrimidin-4- amine (150 mg, 1.04 mmol, 1 equiv), trifluoroacetic acid (480 mg, 4.25 mmol, 4.00 equiv), IPA (5 mL), tert-butyl 4-aminopiperi dine- 1-carboxy late (250 mg, 1.25 mmol, 1.19 equiv). The resulting solution was stirred for 16 h at 90 C in an oil bath. The crude product was purified by Prep-HPLC C NH4HC03. This resulted in 42.2 mg (19%) of N4-methyl-N2- (piperidin-4-yl)pyrimidine-2,4-diamine as light yellow oil.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 01352-01354

45
[ 109-73-9 ]
[ 66131-68-8 ]
N2-butyl-N4-methylpyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
19%	With trifluoroacetic acid; In isopropyl alcohol; at 90℃; for 16h;	Into a 50-mL round-bottom flask, was placed 2-chloro-N-methylpyrimidin-4- amine (150 mg, 1.04 mmol, 1 equiv), butan-1 -amine (80 mg, 1.09 mmol, 1.05 equiv), trifluoroacetic acid (380 mg, 3.36 mmol, 3.00 equiv), IPA (5 mL). The resulting solution was stirred for 16 h at 90 C in an oil bath. The crude product was purified by Prep-HPLC C NH4HCO3. This resulted in 35.1 mg (19%) of N2-butyl-N4-methylpyrimidine-2,4-diamine as white oil. Analytical Data: LC-MS: (ES, m/z): RT = 1.15 min, LCMS 07: m/z = 181.1 [M+l]. 1H NMR (300 MHz, Methanol-d4) delta 7.61 (d, J = 6.0 Hz, 1H), 5.77 (d, J= 6.0 Hz, 1H), 3.34 (t, J= 4.5 Hz, 1H), 3.32 (t, J = 1.5 Hz, 1H), 2.87 (s, 3H), 1.63 - 1.53 (m, 2H), 1.48 - 1.36 (m, 2H), 0.98 (t, J= 7.2 Hz, 3H).

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 01355-01358

46
[ 1158759-06-8 ]
[ 66131-68-8 ]
N4-methyl-N2-(3-methylpiperidin-3-yl)pyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
17%	With trifluoroacetic acid; In isopropyl alcohol; at 90℃; for 16h;	Into a 50-mL round-bottom flask, was placed 2-chloro-N-methylpyrimidin-4- amine (200 mg, 1.39 mmol, 1 equiv), tert-butyl 3-amino-3-methylpiperidine-l -carboxylate (357 mg, 1.67 mmol, 1.20 equiv), trifluoroacetic acid (791 mg, 7.00 mmol, 5.02 equiv), IPA (4 mL). The resulting solution was stirred for 16 h at 90 C in an oil bath. The crude product was purified by Prep-HPLC C NH4HCO3. This resulted in 52.4 mg (17%) N4-methyl-N2-(3- methylpiperidin-3-yl)pyrimidine-2,4-diamine as a light yellow solid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 01359-01361

47
[ 1158759-06-8 ]
[ 66131-68-8 ]
N2-(1-butyl-3-methylpiperidin-3-yl)-N4methylpyrimidine-2,4-diamine [ No CAS ]

Reference： [1]Patent: WO2017/181177,2017,A1

48
[ 66131-68-8 ]
[ 343788-69-2 ]
N4-methyl-N2-(4-methylpiperidin-4-yl)pyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
6%	With trifluoroacetic acid; In isopropyl alcohol; at 90℃; for 16h;	Into a 50-mL round-bottom flask, was placed 2-chloro-N-methylpyrimidin-4- amine (400 mg, 2.79 mmol, 1 equiv), trifluoroacetic acid (1109 mg, 9.81 mmol, 4.00 equiv), IPA (10 mL), tert-butyl 4-amino-4-methy Ipiperi dine- 1-carboxy late (573 mg, 2.67 mmol, 1.10 equiv). The resulting solution was stirred for 16 h at 90 C in an oil bath. The crude product was purified by Prep-HPLC C NH4HCO3. This resulted in 34 mg (6%) of N4-methyl-N2-(4- methylpiperidin-4-yl)pyrimidine-2,4-diamine as a white semisolid.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 01362-01364

49
[ 66131-68-8 ]
[ 343788-69-2 ]
N2-(1-butyl-4-methylpiperidin-4-yl)-N4-methylpyrimidine-2,4-diamine [ No CAS ]

Reference： [1]Patent: WO2017/181177,2017,A1

50
[ 1031335-25-7 ]
[ 66131-68-8 ]
N2-((1R,3S)-3-aminocyclopentyl)-N4-methylpyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
5%	With trifluoroacetic acid; In isopropyl alcohol; at 90℃; for 16h;	Into a 100-mL round-bottom flask, was placed 2-chloro-N-methylpyrimidin-4-amine (300 mg, 2.09 mmol, 1 equiv), trifluoroacetic acid (2.375 g, 21.01 mmol, 10.06 equiv), IPA (5 mL), <strong>[1031335-25-7]tert-butyl N-[(1S,3R)-3-aminocyclopentyl]carbamate</strong> (459 mg, 2.29 mmol, 1.10 equiv). The resulting solution was stirred for 16 h at 90 C in an oil bath. The crude product was purified by Prep-HPLC C TFA. This resulted in 33.2 mg (5%) of N2-((1R,3S)-3-aminocyclopentyl)-N4-methylpyrimidine-2,4-diamine as light yellow oil.

Reference： [1]Patent: WO2017/181177,2017,A1 .Location in patent: Paragraph 01365-01367

51
4-methoxy-3-[1H-pyrrolo[3,2-c]pyridin-6-yl]aniline [ No CAS ]
[ 66131-68-8 ]
[ 76-05-1 ]
N₂-(4-methoxy-3-(1H-pyrrolo[3,2-c]pyridin-6-yl)phenyl)-N₄-methylpyrimidine-2,4-diamine trifluoroacetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20%	In isopropyl alcohol; at 80℃; for 2h;	Into a 50-mL round-bottom flask, was placed 4-methoxy-3-[lH-pyrrolo[3,2-c]pyridin-6- yl]aniline ( 180 mg, 0.75 mmol, 1.00 equiv), <strong>[66131-68-8]2-chloro-N-methylpyrimidin-4-amine</strong> (107 mg, 0.75 mmol, 0.99 equiv), trifluoroacetic acid (171.7 mg, 1.52 mmol, 2.02 equiv), I P A. (5 mL). The resulting solution was stirred for 2 h at 80 C in an oil bath. The crude product was purified by Prep-HPLC with the following conditions :Column: X Select C18, 19*250 mm, 5 um; Mobile Phase A: Water/0, 05% TFA, Mobile Phase B: ACN; Flow rate: 25 niL/min; Gradient: 25% B to 64% B in 15min. This resulted in 67.8 mg (20%) of the title compound as the trifluoroacetic acid salt as a white solid.

Reference： [1]Patent: WO2018/118842,2018,A1 .Location in patent: Paragraph 0601; 0608; 0609

52
[ 66131-68-8 ]
[ 371-40-4 ]
C₁₁H₁₁FN₄ [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2019,vol. 17,p. 2020 - 2027

Same Skeleton Products

Related Products

Historical Records

Related Functional Groups of
[ 66131-68-8 ]

Chlorides

[ 86443-51-8 ]

2-Chloro-N-ethylpyrimidin-4-amine

Similarity: 0.98

[ 7461-50-9 ]

2-Chloropyrimidin-4-amine

Similarity: 0.91

[ 32998-03-1 ]

2,6-Dichloro-N-methylpyrimidin-4-amine

Similarity: 0.85

[ 3569-33-3 ]

2-Chloro-N,6-dimethylpyrimidin-4-amine

Similarity: 0.85

[ 62968-37-0 ]

4-(2-Chloropyrimidin-4-yl)morpholine

Similarity: 0.79

Amines

[ 86443-51-8 ]

2-Chloro-N-ethylpyrimidin-4-amine

Similarity: 0.98

[ 7461-50-9 ]

2-Chloropyrimidin-4-amine

Similarity: 0.91

[ 32998-03-1 ]

2,6-Dichloro-N-methylpyrimidin-4-amine

Similarity: 0.85

[ 3569-33-3 ]

2-Chloro-N,6-dimethylpyrimidin-4-amine

Similarity: 0.85

[ 14394-70-8 ]

2-Chloro-5-methylpyrimidin-4-amine

Similarity: 0.79

Related Parent Nucleus of
[ 66131-68-8 ]

Pyrimidines

[ 86443-51-8 ]

2-Chloro-N-ethylpyrimidin-4-amine

Similarity: 0.98

[ 7461-50-9 ]

2-Chloropyrimidin-4-amine

Similarity: 0.91

[ 32998-03-1 ]

2,6-Dichloro-N-methylpyrimidin-4-amine

Similarity: 0.85

[ 3569-33-3 ]

2-Chloro-N,6-dimethylpyrimidin-4-amine

Similarity: 0.85

[ 62968-37-0 ]

4-(2-Chloropyrimidin-4-yl)morpholine

Similarity: 0.79

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 66131-68-8 ] {[proInfo.proName]}

Quality Control of [ 66131-68-8 ]

Related Doc. of [ 66131-68-8 ]

Product Details of [ 66131-68-8 ]

Calculated chemistry of [ 66131-68-8 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 66131-68-8 ]

Application In Synthesis of [ 66131-68-8 ]

[ 66131-68-8 ] Synthesis Path-Upstream 1~2

[ 66131-68-8 ] Synthesis Path-Downstream 1~52

Related Functional Groups of [ 66131-68-8 ]

Chlorides

Amines

Related Parent Nucleus of [ 66131-68-8 ]

Pyrimidines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 66131-68-8 ]

Related Parent Nucleus of
[ 66131-68-8 ]